{"id":"e1c5bfc8-c6f1-501b-a2ae-0b093716785b","stable_key":"0ad8610d-d575-5870-b7cd-763a9f750783:copper-slc25a3-cox-deficiency","predicate":"loss_impairs","statement":"SLC25A3 knockdown or deletion caused COX deficiency in human and mouse cell models; copper addition suppressed the defects in that study.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"175e16b0-16bd-5536-8842-c5467171f70a","mechanism_event_label":"Getting enough copper to the respiratory enzyme depends on transport machinery.","subject":{"id":"c37d5788-7e5f-5946-8fc6-1dc7f312a1df","slug":"slc25a3","display_name":"Human mitochondrial phosphate/copper carrier SLC25A3","entity_type_key":"protein"},"object":{"id":"7a6f5c2d-cf51-5638-8d69-37355ca6f9d7","slug":"respiratory-complex-iv","display_name":"Mitochondrial cytochrome c oxidase / respiratory complex IV","entity_type_key":"protein_complex"},"evidence_count":1,"mechanism_event":{"id":"175e16b0-16bd-5536-8842-c5467171f70a","stable_key":"0ad8610d-d575-5870-b7cd-763a9f750783:copper-slc25a3-cox-deficiency-event","event_type":"biochemical_relationship","label":"Getting enough copper to the respiratory enzyme depends on transport machinery.","description":"SLC25A3 knockdown or deletion caused COX deficiency in human and mouse cell models; copper addition suppressed the defects in that study.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"c37d5788-7e5f-5946-8fc6-1dc7f312a1df","slug":"slc25a3","display_name":"Human mitochondrial phosphate/copper carrier SLC25A3","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"7a6f5c2d-cf51-5638-8d69-37355ca6f9d7","slug":"respiratory-complex-iv","display_name":"Mitochondrial cytochrome c oxidase / respiratory complex IV","entity_type_key":"protein_complex"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/copper-research/29237729.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1\", \"start_char\": 0, \"end_char\": 1292, \"text_sha256\": \"d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Carrier perturbation, yeast complementation, bacterial transport and reconstituted liposomes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"SLC25A3 loss or reconstitution; extracellular copper addition","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The study established copper transport and COX dependence; later export findings extend rather than negate this work. Rescue conditions differ between experiments.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Copper research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"copper","display_name":"Copper","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Human and mouse cells; heterologous yeast and Lactococcus assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Getting enough copper to the respiratory enzyme depends on transport machinery.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[copper-p29237729] The mammalian phosphate carrier SLC25A3 is a mitochondrial copper transporter required for cytochrome c oxidase biogenesis. (2018). https://pubmed.ncbi.nlm.nih.gov/29237729/ DOI: 10.1074/jbc.ra117.000265","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Inner mitochondrial membrane","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"093b39a3-92fe-5627-9d7c-5fcae9f4c5b8","evidence_kind":"source_excerpt","locator":"Lines 533-544","start_line":533,"end_line":544,"excerpt":"### copper-slc25a3-cox-deficiency\nSLC25A3 knockdown or deletion caused COX deficiency in human and mouse cell models; copper addition suppressed the defects in that study.\nCondition category: machinery_impairment\nnutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Getting enough copper to the respiratory enzyme depends on transport machinery.\norganism: Human and mouse cells; heterologous yeast and Lactococcus assays\ntissue_or_cell_type: Inner mitochondrial membrane\nexperimental_model: Carrier perturbation, yeast complementation, bacterial transport and reconstituted liposomes\nlimitations: The study established copper transport and COX dependence; later export findings extend rather than negate this work. Rescue conditions differ between experiments.\nexposure: SLC25A3 loss or reconstitution; extracellular copper addition\nevidence_span: {\"source_cache\": \"artifacts/copper-research/29237729.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1\", \"start_char\": 0, \"end_char\": 1292, \"text_sha256\": \"d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1\"}\n[copper-p29237729] The mammalian phosphate carrier SLC25A3 is a mitochondrial copper transporter required for cytochrome c oxidase biogenesis. (2018). https://pubmed.ncbi.nlm.nih.gov/29237729/ DOI: 10.1074/jbc.ra117.000265","model_system":"Carrier perturbation, yeast complementation, bacterial transport and reconstituted liposomes","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [copper-p29237729] The mammalian phosphate carrier SLC25A3 is a mitochondrial copper transporter required for cytochrome c oxidase biogenesis. (2018). https://pubmed.ncbi.nlm.nih.gov/29237729/ DOI: 10.1074/jbc.ra117.000265","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"9afba495-cbdc-51aa-998e-70a930dba3be","stable_key":"import-0ad8610d-d575-5870-b7cd-763a9f750783","title":"Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"84b0f62b2dae6835fa26902be87625c003c6c707492d3007e8f9d15420669008","revision_id":"d7e35b8b-3f77-56d9-90b5-5f542c63f321","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}